AβPP-induced UPR Transcriptomic Signature of Glial Cells to Oxidative Stress as an Adaptive Mechanism to Preserve Cell Function and Survival.

Background: Alzheimer's disease (AD) and age-related macular degeneration (AMD) present similarities, particularly with respect to oxidative stress, including production of 4-Hydroxy-2- nonenal (HNE). AMD has been named the AD in the eye. The Müller cells (MC) function as a principal glia of the retina and maintain water/potassium, glutamate homeostasis and redox status.

Technological approaches to minimize industrial trans fatty acids in foods.

Trans fatty acids (TFAs) mainly arise from 2 major sources: natural ruminal hydrogenation and industrial partial catalytic hydrogenation. Increasing evidence suggests that most TFAs and their isomers cause harmful health effects (that is, increased risk of cardiovascular diseases). Nevertheless, in spite of the existence of an international policy consensus regarding the need for public health action, several countries (for example, France) do not adopt sufficient voluntary approaches (for example, governmental regulations and systematic consumer rejections) nor sufficient industrial strategies (for example, development of healthier manufacturing practices and innovative processes such as fat interesterifications) to eliminate deleterious TFAs from processed foods while ensuring the overall quality of the final product (for example, nutritional value and stability).

Trans-fatty acids, dangerous bonds for health? A background review paper of their use, consumption, health implications and regulation in France.

Introduction: Trans-fatty acids (TFAs) can be produced either from bio-hydrogenation in the rumen of ruminants or by industrial hydrogenation. While most of TFAs' effects from ruminants are poorly established, there is increasing evidence that high content of industrial TFAs may cause deleterious effects on human health and life span.

Material And Methods: Indeed, several epidemiological and experimental studies strongly suggest that high content of most TFA isomers could represent a higher risk of developing cardiovascular diseases by a mechanism that lowers the "good HDL cholesterol" and raises the "bad LDL cholesterol.

Distinct effects of inflammation on gliosis, osmohomeostasis, and vascular integrity during amyloid beta-induced retinal degeneration.

In normal retinas, amyloid-β (Aβ) accumulates in the subretinal space, at the interface of the retinal pigment epithelium, and the photoreceptor outer segments. However, the molecular and cellular effects of subretinal Aβ remain inadequately elucidated. We previously showed that subretinal injection of Aβ(1-42) induces retinal inflammation, followed by photoreceptor cell death.

CCR2/CCL2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosis.

Age-related macular degeneration is characterized by the formation of drusen containing amyloid-β (Aβ) and the degeneration of photoreceptors. To explore the largely unknown role of Aβ in the retina, we investigated the effects on photoreceptors of the oligomeric form of Aβ(1-42). Subretinal injection of the Aβ peptide induced misplaced expression of recoverin and synaptophysin in the photoreceptors, oxidative stress in their inner and outer segments, and finally apoptosis.

Prematurely senescent ARPE-19 cells display features of age-related macular degeneration.

The etiology of age-related macular degeneration (AMD), the leading cause of blindness in the developed world, remains poorly understood, but may be related to cumulative oxidative stress. The prime target of the disease is the retinal pigmented epithelium (RPE). To study the molecular mechanisms underlying RPE degeneration, we investigated whether repetitive oxidative stress induced premature senescence in RPE cells from the human ARPE-19 cell line.

Sustained versus transient ERK1/2 signaling underlies the anti- and proapoptotic effects of oxidative stress in human RPE cells.

Purpose: Oxidative stress is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), which involves retinal pigmented epithelial (RPE) cell death. However, signaling pathways involved in the oxidative-stress-induced RPE cell death are poorly understood. This study was conducted to investigate the involvement of the MAP kinase pathways during the induction of RPE cell death by oxidative stress.

[The teaching of the biology of ageing in France 1990-2005: DEA with the course of speciality of Master Seeks].

In 1990, following an idea arising from an Inserm study section on aging, the Diplôme d'études approfondies (DEA) de Biologie du vieillissement was created. Since then, more than 300 students have followed these courses which cover the cellular mechanisms of aging and associated diseases, from basic causes of aging to CNS and sensory organs aging, as well as nutritional aspects, sarcopenia and osteoporosis, vascular and neuroendocrine aging. More than 150 thesis have been defended and more than a quarter of students has been recruited on permanent positions in French universities and research institutions (10 %) and hospitals (16 %).

A new challenge for diabetologists and geriatricians!

The "Société Française de Gériatrie et Gérontologie" (SFGG) and "Association de Langue Française pour l'Etude du Diabète et des Maladies Métaboliques" (ALFEDIAM) have decided to join their efforts in actions to improve the management and treatment of the elderly diabetic patients. New knowledge brought by the fundamental research in the domains of longevity genes made possible to discover genetic ways, like IGF-1 (insulin-like growth factor 1) which play a regulating role between adequacy of the external food availabilities and nutritional body needs. Others discovery in the field of the epigenetic regulation of the nutrition have consequences on pathology such as the metabolic syndrome.

[Fundamental aspects of extreme aging].

Major developments in molecular biology in invertebrates have recently shown the determining effect of genetics on aging. The first finding was that artificial selection can highlight the genetic aspect of the aging process, demonstrating the polygenetic property of longevity. Another finding showed that certain gene transfers can modulate the lifespan of an organism.

A caspase-independent cell clearance program. The LEI/L-DNase II pathway.

The discovery of caspase-mitochondrial pathway counts as one of the most important discovery in apoptosis biochemistry. Today, however, we begin to recognize its limits. Inhibition of caspase does not prevent cell death in many mammalian models.

L-DNase II, a molecule that links proteases and endonucleases in apoptosis, derives from the ubiquitous serpin leukocyte elastase inhibitor.

The most widely recognized biochemical change associated with the majority of apoptotic systems is the degradation of genomic DNA. Among the enzymes that may participate in this cleavage, the acidic cation-independent DNase II is a likely candidate since it is activated in many apoptotic cells. To better understand its role, we purified and sequenced a DNase II extracted from porcine spleen.

Accumulation of mitochondrial DNA deletions in human retina during aging.

Purpose: The authors investigated the presence of mitochondrial DNA (mtDNA) mutations in aging human retina.

Methods: A quantitative polymerase chain reaction technique for studying the common mtDNA 4977-deletion (delta mtDNA4977) in retinal pigment epithelium (RPE) and neural retinal (NR) was developed.

Results: Although no deletion was detected in the fetus, every adult RPE and NR had this common deletion.

Multiple deletions in mitochondrial DNA are present in senescent mouse brain.

We report for the first time that multiple deletions occur during ageing of mice brain mitochondrial DNA (mtDNA). Deletions were detected by electrophoresis after amplification using the nested Polymerase Chain Reaction (N-PCR) method. Three mutant mtDNAs with 3726-, 3867- and 4236-bp deletions were directly detected by N-PCR which were undetectable in young brain mice.

FRAR course on laboratory approaches to aging. Cellular aging, in vitro and in vivo.

Human cells grown in culture exhibit exponential growth provided they are regularly provided with fresh medium. This exponential growth is limited, and although the cells eventually cease to divide, they remain viable for long periods of time. Such a culture is deemed to be "senescent", but it is not clear whether this reflects the growth pattern of cells in vivo.

Differential localization by in situ hybridization of specific crystallin transcripts during mouse lens development.

The embryonic development of the mammalian lens is well known at the biochemical and histological level. However few data are available at the molecular level concerning gene expression during the continuous differentiation of the lens. In the present study, we have investigated by in situ hybridization the changes in the distribution of mouse crystallin mRNA as a marker of differentiated lens cells, during development of the lens primordium, when tissue interactions are known to be essential.

A senescence up-regulated protein: the rat thyroxine-binding globulin (TBG).

Thyroxine-binding globulin (TBG), the major carrier of thyroid hormones in human serum, was thought to be absent in most species, including rodents. We demonstrated recently that in fact the rat possesses a TBG gene, virtually non-expressed in young adults, but actively transcribed during post-natal development. We now find that the TBG gene is also increasingly re-expressed during senescence.

Biomarkers of aging.

This paper summarises a conceptual discussion of some aspects of biomarkers of aging and the logical strategy for developing them. A biomarker of aging is a biological parameter of an organism that either alone or in some multivariate composite will, in the absence of disease, better predict functional capability at some late age than with chronological age. The criteria for putative biomarker measurement and assessment of putative biomarkers are discussed.

Evidence for a relationship between longevity of mammalian species and a lens growth parameter.

The lens growth was studied in a number of curves representing 16 mammalian species. Emphasis was placed on determining the length of the lens development stage. All the lens curves studied went through a growth crisis: It is a period of apparent growth slowing down, lasting linear during the resting lifespan (adult stage).

Variation in the relative abundance of gamma-crystallin gene transcripts during development and ageing.

The transcripts of gamma-crystallin mRNA were examined during adulthood. The mRNA transcripts were detected by Northern blot technique. Although the total RNA per lens measured remains constant during adulthood, the mRNA transcript size was observed to decline with ageing, specifically for the gamma-crystallin and not for alpha- and beta-crystallins.

Gamma-crystallin family of the mouse lens: structural and evolutionary relationships.

The heterogeneity inherent among gamma-crystallins of the mouse lens was investigated by sequence analysis of three gamma-crystallin-specific cDNAs. Comparison of the nucleotide sequence of these cDNAs and one previously reported by us revealed that the four gamma-cDNAs share 80-90% homology in nucleotide sequence. The entire 3' half of the coding region shows more variability than the 5' half, whereas the greatest variability is observed in the 3' untranslated region where numerous base substitutions, deletions, and insertions seem to have occurred.

Evidence against gamma-crystallin DNA or RNA sequences in the chicken.

A cloned cDNA (pM gamma 1 Crl) encoding about two-thirds of a gamma-crystallin polypeptide from the murine lens was used as a hybridization probe to search for the presence of gamma-crystallin-like RNA or DNA sequences in the chicken. The 15-day-old chicken lens did not contain any RNA sequences homologous to the murine gamma-crystallin cDNA, as judged by Northern blot hybridization. An approximate 2.

Analysis of the rat lens epithelial cell nucleus during ageing by scanning cytophotometry.

Nuclei of rat lens epithelial cells were stained with eosin and hematoxylin in order to investigate by cytophotometric analysis the effects of cellular ageing on their morphologic parameters and chromatin compaction. Our results demonstrate a decrease in the size of the nucleus without modification in their shape as a function of age. Older nuclei also have more condensed and heterogeneously distributed chromatin than young nuclei.